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Hi, I'm Doctor Buddy Creech, and I'm a pediatric infectious diseases physician here in Nashville, Tennessee. And today, we're gonna talk a little bit about the management of high-risk pediatric COVID-19 patients. Uh, thankfully, the pandemic is over. Uh, we're still living through the PTSD of all of that. But there's still work to be done. This is still a significant respiratory virus for many of our patients. And so today, what we're gonna talk about is how to stratify those kids that are in high-risk categories, how to prioritize their testing, and then what we have both for treatment as well as prevention of severe disease in these kids. Uh, to get started, let me just say I do have some potential conflicts of interest. I received grant funding from the NIH and from the CDC as well as from Pfizer vaccines for a C. difficile vaccine clinical trial. I serve on the data and safety monitoring boards for a, a couple of companies for two specific studies. And then I serve as a consultant to a variety of groups really for the purpose of developing new vaccines and new antibiotics and making sure that the ones we have are safe and effective. With that being said, let me tell you what I think our goals of the session are today. Uh, the first and foundational goal is to really identify those patients who are at high risk for severe COVID-19 disease. Uh, the second is to develop treatment plans for different patient groups and levels of disease severity. And then third is to know the two primary strategies for the prevention of severe COVID-19 and then the sequelae of COVID-19. And, and here's the bottom line upfront. First, most pediatric COVID-19 cases are mild. I think this is important for us to acknowledge and to probably lead with, with families because they know they're mild, we know they're mild, and it's OK to acknowledge that. But I think as soon as we say that, we also have to put in an incredibly important caveat, which is some children and adolescents are at particular risk for severe disease or for the complications associated with COVID-19. And while some of these may be more significant, like myocarditis or blood clots, some are more vague or more difficult to understand, like long COVID or the post-acute sequela of COVID. So third, the other bottom line is we want to be able to identify high-risk patients because that will enable us to have more effective prevention and management strategies, including vaccines and, and antiviral therapy. So let's get started with the first foundational element, which is who should be considered high risk for COVID-19 disease severity. And I think we're aided here by a really nice paper from the Journal of the Pezz ID Society, um, where they looked at nearly 200,000 children and adolescents who were included in this systematic review and meta-analysis. And it's important to recognize that in previously healthy children, those without any comorbidities, the absolute risk from COVID-19 for severe or critical disease was only about 4%. Now, that may not seem like a lot, but when we go through periods of high outbreak potential, or we have these clusters of increased activity in our communities, that 4% can be significant. But I think the important thing they added were what were the risk factors for the kids who needed hospitalization, who needed critical care, who had, who had complications from COVID-19. Just a busy slide. We're gonna unpack it. We'll zoom in on a couple of areas, but I wanna highlight a couple of things. On the left are different characteristics found in this cohort. Um, and the columns are either bar graphs or the absolute numerical numbers represented by those. In the third, you'll see these diamonds with whiskers around them. Those are an idea of what the relative risk is compared to healthy kids, um, where the, the diamond represents what the estimate is, and then the whisker represents how confident we are. That's the 95% confidence. And you see a straight line down the screen, that's one. So, anything to the left of that straight line would be protective. Anything to the right would be increased risk compared to healthy children. And then on the far right, you see numbers like 1.09, 2.39. These are numbers saying that this is the risk and the confidence around it. Again, anything over 1 would be an increase. So if you have a 2, that's a doubling of the risk. If you have a 1.5, that would be a 50% increased risk. So, let's zoom in on a couple of things. The first is demographics. Age less than 1 year, particularly age less than 1 month, were both, those were both associated with an increased likelihood of severe disease. And what's that numerical value? Well, age less than 1 year actually wasn't statistically significant. So, a 9 month old, a 10 month old, the point estimate was increased, but not by much, and the confidence interval goes both sides of one. So this really isn't a terrible increased risk, but look at those who are less than a month of age. That relative risk is 2.39, meaning kids in their first month of life, if they get infected with COVID, they're more than twice as likely to have severe disease. Next, we can look at things like the comorbidities below, whether that's cardiovascular disease, neurologic conditions. chronic GI conditions, chronic kidney disease, or diabetes. All of these are associated with very high increased relative risk of severe disease. Uh, interestingly, rheumatologic conditions and things like asthma weren't. Um, but if you look at pulmonary diseases other than asthma, there's a significant increase. So, the summary of this work, outside of just those individual comorbidities that we can risk stratify based on, we can say the following. In the presence of one comorbidity, children are about 4 times more likely to have severe COVID. And if you have 2 or more comorbidities, children were nearly 10 times more likely to have severe COVID. What does that mean for us in our practice? It means we probably need to prioritize vaccination. And really encourage it for, for all who want to be protected. And we've really got to take extra steps to make sure those with underlying comorbidities are protected through vaccination. Here's another way to look at this, maybe in a more simplified way. The risk factors on the left, the pooled odds ratio is on the right. You can see that those elements that were the most predictive of severe disease were young age, cardiovascular, neuro, GI, and kidney disease, diabetes, obesity, which we recognize the current epidemic of obesity that we have in the country, immunocompromised states, pulmonary conditions that weren't asthma, and then asthma is actually lower. Now, this should not discourage us from vaccinating. Our kids with COVID, um, who have asthma. Uh, not at all. But what it does recognize is that if we have an asthmatic who for some reason refuses to be vaccinated, we recognize that the risk for them is maybe a little bit lower than the risk for other pulmonary conditions like those who are trait dependent or who have cystic fibrosis or other underlying pulmonary diseases. I think the reason all of this is important is that over 45% of children that are 3 to 17 years of age in the United States have at least one chronic medical condition, and yet only about 20, maybe 15% in some of our areas of children have been boosted and are receiving updated vaccines against COVID. So we have a discrepancy here between the number of children who have underlying comorbidities and those who are being vaccinated. We want to try to close that gap. So how do we stratify the risk? Well, we stratify it based on conditions that increase the risk to most respiratory viruses. This would be congenital heart disease, chronic lung disease, neurologic disorders, and immunocompromising states. And the idea here is that we should be very holistic in how we approach this. We should be recommending COVID vaccine and influenza vaccine in order to protect them. The second are conditions that disproportionately increase the risk for COVID-19 severity, and, and those might be lumped into categories like obesity or type 1 diabetes, where inflammation is a cardinal piece of the pathogenesis. And then the third are just miscellaneous things like substance use disorders and smoking, all of which increase the risk, not only for COVID-19 in some situations, but also respiratory viruses and in some situations, bacterial infections as well. So, here are 3 practice recommendations based on this. Number 1, recommend that patients with medical comorbidities receive COVID vaccine through shared decision making and anticipatory guidance. I think this is important. The second is to recommend respiratory viral testing, especially flu and COVID, in patients with medical comorbidities. Most patients don't want to come to the doctor or to a nurse practitioner or any other healthcare provider when they're sick. They'd rather just stay at home. But we need to also recognize that if we don't know what the patient has, it's hard to treat them. And so, if we can get them to the point of testing, we probably can give them more pathogen-directed therapy. So, that brings up number 3, which is to initiate antiviral therapy as needed to reduce the likelihood of complications from COVID. So, that's 3 practice recommendations that I think are very uh actionable.